4. Airways Function Flashcards
Outline the basic structure and organisation of the airways
Airways are either cartilaginous or alveolar
Their basic function is to either act as conduit pipes or to conduct gas exchange
Their function is facilitated by mechanical stability (cartilage) and control of calibre (smooth muscle)
There are 23 generations of branching from trachea to alveolar sacs, consisting of a conducting, transitional and respiratory zone, where cartilage quantity decreases and smooth muscle increases
Cartilage ring incomplete and slightly offset, but smooth muscle and nervous innervation complete
Name and describe the different categories of cells contained within the airways
Lining – ciliated, intermediate, brush and basal
Contractile – smooth muscle
Secretory – goblet (epithelium), mucous, serous (glands)
Connective – fibroblasts, interstitial (elastin, collagen, cartilage)
Neuroendocrine – nerves, ganglia, neuroendocrine, neuroepithelial bodies
Vascular – endothelial, pericyte, plasma
Immune – mast, dendritic, lymphocyte, eosinophil, macrophage, neutrophil
Outline the structure of the human airway epithelium
Consists of ciliated epithelial cells with goblet cells protruding through the layer into the lumen of the airway
Mitochondria also prominent
Goblet cells contain mucin granules; these contain mucin in a highly condensed form
Upon secretion, intra-granular mucin expands using ATP absorbing water and swelling
Outline the submucosal glands
Acini are functional units of secretory cells present in airways
Mucous cells secrete mucus
Serous cells secret antibacterials e.g. lysozyme
Glands also secrete water and salts e.g. Na+ and Cl-
Define ‘acinus’
1) A small sac-like cavity in a gland, surrounded by secretory cells
2) A region of the lung supplied with air from one of the terminal bronchioles
Outline human ciliary structure
Apical hook engages with mucus
‘9 + 2’ arrangement allows movement of cilia
~200 per ciliated cell
Cilia beating – engages with mucus when vertical, but otherwise circles back (so as to prevent mucus just being moved back and forth)
Outline airway epithelial function
Secretion of mucins, water and electrolyte components of ‘mucus’ (and plasma, mediators etc.)
Movement of mucus by cilia – mucociliary clearance
Physical barrier to foreign substances
Production of regulatory and inflammatory mediators:
o NO (by nitric oxide synthase, NOS) o CO (by hemeoxygenase, HO) o Arachidonic acid metabolites, e.g. prostaglandins (COX) o Chemokines, e.g. interleukin (IL)-8 o Cytokines, e.g. GM-CSF o Proteases
Outline the function of airway smooth muscle
Inflammation affects the structure, airway calibre and secretory effects of smooth muscle cells within airways
Structural effects – hypertrophy
Airway calibre (tone) – contractile and relaxation effects
Secretion – mediators, cytokines, chemokines
o Bacterial products stimulate:
- NOS –> NO release
- COX –> prostaglandin release
- Cytokine, chemokine and adhesion molecule release –> inflammatory cell recruitment
Outline the trachea-bronchial circulation in terms of airway vasculature
Comprises 1-5% of cardiac output
Blood flow to airway mucosa = 100-150 ml/min/100g tissue (amongst the highest to any tissue)
Bronchial arteries arise from many sites on: aorta, intercostal arteries and others
Blood returns from tracheal circulation via systemic veins
Blood returns from bronchial circulation to both sides of heart via bronchial and pulmonary veins
Outline the functions of the airway vasculature
Good gas exchange (airway tissues and blood)
Contributes to the warming of inspired air
Contributes to the humidification of inspired air
Clears inflammatory mediators
Clears inhaled drugs (good/bad, depending on drug)
Supplies airway tissue and lumen with inflammatory cells
Supplies airway tissue and lumen with proteinaceous plasma (‘plasma exudation’); inflammatory mediators (e.g. histamine, platelet activating factor - PAF) transported in the blood to endothelial cells, which stimulates the release of plasma into the layer of epithelial cell
Outline the control of airway function
Nerves:
o Parasympathetic – cholinergic
o Sympathetic – adrenergic
o Sensory innervation
Regulatory and inflammatory mediators:
o Histamine
o Arachidonic acid metabolites (e.g. prostaglandins, leukotrienes)
o Cytokines
o Chemokines
Proteinases (e.g. neutrophil elastase)
Reactive gas species (e.g. O2-, NO)
Outline the innervation of the airways
Parasympathetic motor pathway (cholinergic) –> constriction via the vagus nerve
Sensory innervation to the brainstem via the nodose ganglion (inferior ganglion of the vagus nerve); also via the dorsal root ganglion to the spinal cord
Sympathetic innervation from the spinal cord via the cervical thoracic ganglion (relaxation); adrenaline from adrenal gland also, leading to relaxation
Outline cholinergic mechanisms with regards to the airways
Parasympathetic innervation of submucosal glands, smooth muscle cells (and blood vessels)
Muscarinic receptors involving acetylcholine
Activation leads to mucus secretion, airway smooth muscle contraction (and vasodilation)
Outline the regulatory-inflammatory cells in the airways
Cells: eosinophil, neutrophils, macrophages, mast cells, T-lymphocytes
Mediators: histamine, serotonin, adenosine, prostaglandins, leukotrienes, thromboxane, PAF, endothelin, cytokines, chemokines, growth factors, proteinases, reactive gas species
Effects: smooth muscle (both airway and vascular –> constriction and relaxation), secretion (mucus, water etc.), plasma exudation, neural modulation, chemotaxis, remodelling
Note: cells produce more than one mediator, and each mediator has more than one effect
Summarise the clinical correlates of respiratory diseases with loss of airway ‘control’
Asthma, COPD, cystic fibrosis
All common conditions
Cause airway inflammation and obstruction
Also leads to airway remodelling
Outline asthma
A clinical syndrome characterised by increased airway responsiveness to a variety of stimuli (leading to airway obstruction)
Airflow obstruction varies over short periods of time and is reversible (spontaneously or with drugs)
Dyspnoea, wheezing and cough (varying degrees - mild to severe)
Airway inflammation leads to airway re-modelling; a mucous ‘plug’ forms in the lumen, the basement membrane thickens, epithelial cells become more fragile, etc.
Bronchoconstriction occurs; the airway wall is thrown into fold, and mucous plugs into the lumen
Outline COPD
Chronic Obstructive Pulmonary Disease (COPD) is an umbrella term used to describe progressive lung diseases including emphysema, chronic bronchitis, refractory (non-reversible) asthma, and some forms of bronchiectasis
This disease is characterized by increasing breathlessness
How are COPD and asthma distinguished from one another
COPD is an umbrella term for progressive lung diseases, and the symptoms are very similar to asthma
Airway obstruction occurs with both diseases; the age of initial presentation is often the distinguishing feature between COPD and asthma; people who have asthma are typically diagnosed as children
They also both have different causes; experts aren’t sure why some people get asthma, while others do not; it is possibly caused by a combination of environmental and inherited (genetic) factors; it is known that exposure to certain kinds of substances (allergens) can trigger allergies
The known cause of COPD in the developed world is smoking; in developing countries, it’s caused by exposure to fumes from burning fuel for cooking and heating
Outline neutrophil elastase
Neutrophil elastase is a serine proteinase in the same family as chymotrypsin and has broad substrate specificity
Secreted by neutrophils and macrophages during inflammation, it destroys bacteria and host tissue
It also localises to Neutrophil extracellular traps (NETs), via its high affinity for DNA, an unusual property for serine proteases
Neutrophil elastase is an important protease enzyme that when expressed aberrantly can cause emphysema or emphysematous changes; this involves breakdown of the lung structure and increased airspaces; mutations of the ELANE gene cause severe congenital neutropenia, which is a failure of neutrophils to mature
In order to minimise damage to tissues, there are few inhibitors of neutrophil elastase; one group of inhibitors are the Serpins (Serine Protease Inhibitors); neutrophil elastase has been shown to interact with Alpha 2-antiplasmin, which belongs to the Serpin family of proteins
Define airway remodelling
Airway remodeling refers to the structural changes that occur in both the large and the small airways of miscellaneous diseases, including asthma
